The nucleus accumbens has been proposed to be the interface between the limbic and motor systems, and this structure plays a critical role in mediating the reinforcing and rewarding effects of drugs of abuse, as well as sexual experience and food. Dopamine (DA) transmission to the nucleus accumbens subserves these functions. Estrogen has been shown to potently modulate the mesolimbic DA system but the mechanism for this modulation is not well understood. Key modulators that may play a role in estrogen's actions include the intracellular signaling proteins known as Regulators of G-protein Signaling (RGS) and specifically the RGS9 member of this family. RGS9 is abundant in the nucleus accumbens and has recently been shown to be specifically linked to DA D2 receptor mediated effects. Therefore, I propose to investigate estrogenic action in the nucleus accumbens and its modulation of DA signaling. My studies will also assess the changes in reward salience elicited by estrogen using the conditioned place preference paradigm. Data collected will provide important evidence for estrogen's role in the modulation of the nucleus accumbens reward system and drugs of abuse.